RT Journal Article SR Electronic T1 Dynorphin A1–17-Induced Feeding: Pharmacological Characterization Using Selective Opioid Antagonists and Antisense Probes in Rats JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 513 OP 518 DO 10.1124/jpet.301.2.513 VO 301 IS 2 A1 Robert M. Silva A1 Henya C. Grossman A1 Maria M. Hadjimarkou A1 Grace C. Rossi A1 Gavril W. Pasternak A1 Richard J. Bodnar YR 2002 UL http://jpet.aspetjournals.org/content/301/2/513.abstract AB Ventricular administration of the opioid dynorphin A1–17induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. Dynorphin-induced feeding was significantly reduced by a wide range of doses (5–80 nmol i.c.v.) of the selective κ1-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the κ-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding, whereas a missense oligodeoxynucleotide control probe was ineffective. Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the κ3-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective μ-antagonist β-funaltrexamine (20–80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the μ-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor δ (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducing dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the δ-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the κ1-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding. The American Society for Pharmacology and Experimental Therapeutics